CD44, a therapeutic target for metastasising tumours
Section snippets
The cell adhesion protein family CD44
Together with the selectins, the integrins and the cadherins, CD44 transmembrane glycoproteins form part of the huge family of cell adhesion molecules (CAMs). The CAMs control cell behaviour by mediating contact between cells or between cells and the extracellular matrix and are therefore essential for maintaining tissue integrity. Because of these important functions they are prone to be involved in pathological conditions including tumour progression and metastasis. One of the most striking
Importance of CD44 variants in metastasis
CD44 proteins regulate growth, survival, differentiation and migration and are thereby prone to be involved in tumour progression and metastasis. The first major finding involving CD44 in the metastatic process was the identification of a CD44 variant isoform containing the exons v4–v7 in a highly metastasizing rat pancreatic carcinoma cell line (BSp73ASML). Transfection of this specific variant into the related BSp73AS cells that do not metastasize conferred the metastatic potential to these
Influence of HA binding on metastasis
As mentioned in the introduction, the main property ascribed to CD44 is its ability to bind HA. For this reason, this was the first function of CD44 that was believed to be important for the metastatic process. However, despite intensive research, the data are still contradictory. One attempt to elucidate the role of HA binding to CD44 in tumour progression was made with the pancreatic carcinoma cells BSp73AS transfected with the CD44v4–v7 isoforms that conferred the metastatic potential.7
Outlook
There is ample evidence that CD44 isoforms and specifically the CD44v6 isoforms are involved in the metastatic process. Several studies show that the function of CD44 as an HA binding protein is crucial for tumour progression, although this seems not to be a common feature for all tumours. Furthermore, the co-receptor function of CD44v6 for c-Met and also for VEGFR-2 might be crucial for the establishment of primary tumours as well as for metastasis, at least in pancreatic carcinoma. For these
Conflict of interest statement
None declared.
References (49)
- et al.
Heparan sulfate proteoglycan isoforms of the CD44 hyaluronan receptor induced in human inflammatory macrophages can function as paracrine regulators of fibroblast growth factor action
J Biol Chem
(2000) - et al.
A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells
Cell
(1991) - et al.
CD44 variant isoforms in non-Hodgkin’s lymphoma: a new independent prognostic factor
Blood
(1995) - et al.
Prognostic value of CD44 splice variants in human stage III cervical cancer
Eur J Cancer
(1995) - et al.
Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma
Oral Oncol
(2008) The metastasis gene osteopontin: a candidate target for cancer therapy
Biochim Biophys Acta
(2001)- et al.
A strong expression of CD44–6v correlates with shorter survival of patients with acute myeloid leukemia
Blood
(1998) - et al.
CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow
Blood
(2004) - et al.
A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis
Blood
(2009) - et al.
CD44: from adhesion molecules to signalling regulators
Nat Rev Mol Cell Biol
(2003)
CD44 isoforms containing exon v3 are responsible for the presentation of heparin-binding growth factor
J Cell Biol
Mouse T lymphoma cells contain a transmembrane glycoprotein (GP85) that binds ankyrin
J Cell Biol
ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons
J Cell Biol
A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility
Nat Cell Biol
Prevention of tumor metastasis formation by anti-variant CD44
J Exp Med
CD44 in cancer
Crit Rev Clin Lab Sci
Expression of CD44 is repressed in neuroblastoma cells
Mol Cell Biol
CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13
Cancer Res
CD44 and CD44v6 downregulation in clinical prostatic carcinoma: relation to Gleason grade and cytoarchitecture
Prostate
CD44 glycoproteins in colorectal cancer: expression, function, and prognostic value
Adv Cancer Res
Molecular studies into the role of CD44 variants in metastasis in gastric cancer
Mol Pathol
Heparanase, hyaluronan, and CD44 in cancers: a breast carcinoma perspective
Cancer Res
CD44v6: a target for antibody-based cancer therapy
Cancer Immunol Immunother
Evaluation of limited blood sampling in a preceding 99mTc-labeled diagnostic study to predict the pharmacokinetics and myelotoxicity of 186Re-cMAb U36 radioimmunotherapy
J Nucl Med
Cited by (398)
Enhancement of the efficacy of synthetic and natural anticancer agents through nanocarrier for colon cancer treatment
2024, European Journal of Medicinal Chemistry ReportsUnderstanding the role of endothelial cells in brain tumor formation and metastasis: a proposition to be explored for better therapy
2023, Journal of the National Cancer CenterHyaluronic acid-based drug delivery systems for targeted cancer therapy
2023, Natural Biopolymers in Drug Delivery and Tissue EngineeringMultifunctional nanoparticles recruiting hyaluronic acid ligand and polyplexes containing low molecular weight protamine and ATP-Sensitive DNA motif for doxorubicin delivery
2022, Journal of Drug Delivery Science and TechnologyFunctionalized niosomes as a smart delivery device in cancer and fungal infection
2022, European Journal of Pharmaceutical Sciences